DESCRIPTION: (Applicant's description) Combinatorial methods for the synthesis of new drug substances require high throughput techniques for evaluation of structure-activity relationships. Microliter plates with immobilized target receptors can rapidly reduce thousands of possibilities to hundreds of candidates. The next level of screening has proven to be more difficult and tedious. The goal of this project is the creation of an on-line screening approach to expedite secondary screening. The new technology involves immobilized bipolymer HPLC columns (IBCs)containing immobilized multiple receptors. Test compounds will be injected onto the IBC and chromatographed using standard HPLC techniques. The compounds will differentially adhere to the IBC according to their relative affinity for the immobilized receptors, i.e. compounds with little or no affinity to their relative affinity will wash through the IBC while those with moderate affinities will be displaced by ones with higher binding constants. The bipolymer-bound compounds will be sequentially displaced using a characterized ligand and the liberated compounds directed on-line into a mass spectrometer. Thus a large series of compounds can be rapidly screened for their relative affinities for the immobilized receptors with concurrent identification of molecular structures. The objective of this project is to develop prototypic IBCs using GABA, and nicotinic receptors. PROPOSED COMMERCIAL APPLICATION: The immobilized bipolymer columns (IBC's) developed in this project represent a new product for use in the pharmaceutical industry. A series of IBC's will be created for use in combinatorial screens and should find a substantial market as part of a high-throughput screen for new drug substances.